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Hyperglycemia Is Associated with Psoriatic Inflammation in Both Humans and Mice

Published on Jun 1, 2019in Journal of Investigative Dermatology6.29
· DOI :10.1016/j.jid.2019.01.029
K. Ikumi1
Estimated H-index: 1
(Nagoya City University),
Mizuyu Odanaka1
Estimated H-index: 1
(Nagoya City University)
+ 8 AuthorsSayuri Yamazaki27
Estimated H-index: 27
(Nagoya City University)
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Abstract
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved insulin secretion. Imiquimod-induced systemic and cutaneous inflammation in mice, with features of human psoriasis, also resulted in hyperglycemia. Although it should be determined if psoriasis-like cutaneous inflammation alone can induce hyperglycemia, imiquimod-treated mice showed impairment of insulin secretion without significant islet inflammation. Administration of anti-IL-17A monoclonal antibody improved hyperglycemia in patients with psoriasis and imiquimod-treated mice with psoriasiform features. These results suggest that hyperglycemia is highly associated with psoriasis, mainly through IL-17.
  • References (42)
  • Citations (1)
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References42
Newest
Published on Sep 1, 2018in Journal of Investigative Dermatology6.29
Diana Herbert4
Estimated H-index: 4
,
Sandra Franz24
Estimated H-index: 24
+ 6 AuthorsAnja Saalbach24
Estimated H-index: 24
In obesity, hypertrophic adipocytes secrete high amounts of adipocytokines, resulting in low-grade inflammation amplified by infiltrating proinflammatory macrophages, oxidative stress, hypoxia, and lipolysis. These chronic proinflammatory conditions support the development of type II diabetes and cardiovascular diseases, but the mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncovered dietary saturated fatty acids (SFAs) as...
Published on Aug 6, 2018in Journal of Experimental Medicine10.89
Krista Stockenhuber1
Estimated H-index: 1
(University of Oxford),
Ahmed N. Hegazy23
Estimated H-index: 23
(University of Oxford)
+ 9 AuthorsHerman Waldmann106
Estimated H-index: 106
(University of Oxford)
Published on Jul 1, 2018in Immunity21.52
Marko Šestan4
Estimated H-index: 4
(University of Rijeka),
Sonja Marinović2
Estimated H-index: 2
(University of Rijeka)
+ 8 AuthorsFelix M. Wensveen18
Estimated H-index: 18
(University of Rijeka)
Summary Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin resistance (IR) in obesity, but the physiological role of this mechanism is unclear. It is also unknown whether and how viral infection induces loss of glycemic control in subjects at risk for developing diabetes mellitus type 2 (DM2). We have found in mice and humans that viral infection caused short-term systemic IR. Virally-induced interferon-γ (IFN-γ) directly targeted skeletal muscle to downregulate th...
Published on Feb 1, 2018in Journal of The American Academy of Dermatology7.10
Marilyn T. Wan3
Estimated H-index: 3
(UPenn: University of Pennsylvania),
Daniel B. Shin24
Estimated H-index: 24
(UPenn: University of Pennsylvania)
+ 3 AuthorsJoel M. Gelfand53
Estimated H-index: 53
(UPenn: University of Pennsylvania)
Background Data evaluating the impact of objectively measured psoriasis severity on type 2 diabetes mellitus (T2DM) risk are lacking. Objective To determine the risk for T2DM in patients with psoriasis compared with that in adults without psoriasis, stratified by categories of directly assessed body surface area (BSA) affected by psoriasis. Methods A prospective, population-based, cohort study from the United Kingdom in which 8124 adults with psoriasis and 76,599 adults without psoriasis were fo...
Published on Jan 1, 2018in Experimental Dermatology2.87
Seon-Pil Jin5
Estimated H-index: 5
(SNU: Seoul National University),
Seong-Joon Koh9
Estimated H-index: 9
+ 6 AuthorsHyun-sun Park3
Estimated H-index: 3
Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison with previous models. IL-10 deficient and wild-type (WT) mice received either imiquimod or vehicle cream for 12 d...
Published on Dec 1, 2017in Scientific Reports4.01
Satoshi Nakamizo13
Estimated H-index: 13
(Kyoto University),
Tetsuya Honda25
Estimated H-index: 25
(Kyoto University)
+ 10 AuthorsFlorent Ginhoux62
Estimated H-index: 62
(Agency for Science, Technology and Research)
Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesit...
Published on Oct 1, 2017in Journal of Investigative Dermatology6.29
Noriko Shimoura2
Estimated H-index: 2
(Kobe University),
Hiroshi Nagai20
Estimated H-index: 20
(Kobe University)
+ 2 AuthorsChikako Nishigori25
Estimated H-index: 25
(Kobe University)
Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders, such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 an...
Published on Sep 1, 2017in The Journal of Allergy and Clinical Immunology
Jason E. Hawkes4
Estimated H-index: 4
(Rockefeller University),
Tom C. Chan6
Estimated H-index: 6
(Rockefeller University),
James G. Krueger92
Estimated H-index: 92
(Rockefeller University)
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell–mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major para...
Published on Mar 1, 2017in Journal of The American Academy of Dermatology7.10
Junko Takeshita14
Estimated H-index: 14
(UPenn: University of Pennsylvania),
Sungat K. Grewal5
Estimated H-index: 5
(UPenn: University of Pennsylvania)
+ 4 AuthorsJoel M. Gelfand53
Estimated H-index: 53
(UPenn: University of Pennsylvania)
Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psor...
Published on Jul 28, 2016in The New England Journal of Medicine70.67
Kenneth B. Gordon57
Estimated H-index: 57
,
Andrew Blauvelt53
Estimated H-index: 53
+ 17 AuthorsDaniel K. Braun20
Estimated H-index: 20
BackgroundTwo phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. MethodsWe randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 pat...
Cited By1
Newest
Published on Jun 1, 2019in Journal of Investigative Dermatology6.29
Louis C.S. Gardner (Newcastle University), Henry J. Grantham1
Estimated H-index: 1
(Newcastle University),
Nj Reynolds35
Estimated H-index: 35
(Newcastle University)
Psoriasis is associated with the metabolic syndrome, an interconnected group of conditions characterized by significant morbidity and mortality, although the causal mechanisms are still under investigation. Ikumi et al. provide evidence of a link—involving IL-17—between psoriasis and hyperglycemia in humans and mice.
View next paperHigh‐fat diet exacerbates imiquimod‐induced psoriasis‐like dermatitis in mice